Risk of breast cancer mutations underestimated for Asian women, study shows

September 11, 2008,

Oncologist Allison Kurian, MD, and her colleagues at the Stanford University School of Medicine were perplexed. Computer models designed to identify women who might have dangerous genetic mutations that increase their risk of breast and ovarian cancer worked well for white women. But they seemed to be less reliable for another ethnic group.

"We've been repeatedly surprised when Asian women who the models predicted would probably not have the mutations do in fact have them," said Kurian. She recently showed that in a head-to-head comparison between whites and Asians, two of the most commonly used models failed in predicting the presence of mutations in almost half of the Asian women studied.

"Doctors and patients should have a higher level of suspicion when using these prediction models in Asian women, because they under-predicted the true number of clinically important mutations," said Kurian. "We may have to consider more subtle patterns of family cancer history when considering genetic testing in this ethnic group."

Kurian, assistant professor of oncology and of health research and policy, is the first author of the research, which was published online in the Journal of Clinical Oncology on Sept 8.

Mutations in two genes - BRCA1 and BRCA2 - are strongly associated with the development of breast or ovarian cancer in carriers. However, not every woman with a family history of cancer or who develops these cancers has these mutations.

To determine who should be tested for the mutations, genetic counselors frequently use computer models that assess specific variables for each woman, such as the number of relatives affected by breast and ovarian cancer, the age of each relative at onset of the condition and how closely the woman is related to her affected relatives. Those women deemed by the models to be likely carriers of these mutations are referred for testing of their BRCA1 and BRCA2 genes.

Kurian and her colleagues used two of the most widely used computer models, named BRCAPRO and Myriad II, to predict the presence of the mutations in 200 white women and 200 Asian-American women at cancer genetics clinics in four locations: Stanford, the University of California-San Francisco, Queen's Medical Center in Honolulu and the British Columbia Cancer Center in Vancouver. They sequenced the BRCA1 and BRCA2 genes of all of the study subjects and compared them to the models' predictions.

The researchers found that the models were highly accurate in predicting the presence of mutations in white women; one program identified 24 of the 25 women with BRCA1 or BRCA2 mutations and the other identified all 25. However, both programs performed much worse in predicting the 49 Asian women in the study sample with mutations. One program predicted that only 25 of the 49 women would carry mutations, while the other recommended testing of 26 women.

"It's clear that these models are far from foolproof," said Kurian, who is also a member of the Stanford Cancer Center. "These results emphasize the need for expert evaluation by a genetics professional to guide all clinical genetic testing."

Because the Asian and white women reported similar numbers of affected relatives on average, it's possible that fewer Asians with the mutations go on to develop cancer. In that case, the family history would be a less accurate way to determine the presence of the mutations. Kurian and her colleagues are collaborating with researchers in Hong Kong to investigate these and other alternatives.

The study results point out the need for further investigation into the genetic variability of different ethnic groups. In addition to previously identified, clinically important mutations of the genes, the researchers identified more "variants of unknown significance" in the BRCA1 and BRCA2 genes of Asian women than in white women.

Many of these variants probably don't have any clinical effect," said Kurian. "We know a lot more about the normal variability of these genes in white women. Many of these variants are probably just normal for members of a particular ethnic group, but we haven't studied enough people in ethnic minority groups to know for sure, and further research needs to be done to distinguish variants of uncertain significance from truly harmful mutations."

Source: Stanford University Medical Center

Explore further: Breast cancer gene does not boost risk of death: study

Related Stories

Breast cancer gene does not boost risk of death: study

January 12, 2018
Young women with the BRCA gene mutation that prompted actress Angelina Jolie's pre-emptive and much-publicised double mastectomy are not more likely to die after a breast cancer diagnosis, scientists said Friday.

FDA approves first drug for tumors tied to breast cancer genes

January 12, 2018
(HealthDay)—The U.S. Food and Drug Administration on Friday approved the first drug aimed at treating metastatic breast cancers linked to the BRCA gene mutation.

New ovarian cancer drug licensed for use

December 21, 2017
A new drug to delay the spread of ovarian cancer, which was developed from UCL research, has been licensed for use in the UK.

Researchers find protein that mediates formation of HER2-driven breast cancer

January 9, 2018
Researchers at the University of Cincinnati College of Medicine have identified for the first time that the estrogen receptor-binding protein MED1 is a critical mediator of HER2-driven breast cancer, identifying it as a potential ...

For women with genetic risk, bi-annual MRI beats mammograms

December 8, 2017
Intensive surveillance including a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) exam every six months was far more effective in detecting breast cancer in younger women with a high-risk genetic profile than ...

Study results offer another boon for PARP inhibitors in treatment of advanced breast cancer

December 8, 2017
Patients with certain advanced hereditary breast cancers may have new treatments options on the horizon, according to two studies presented this week at the annual San Antonio Breast Cancer Symposium. Susan Domchek, MD, executive ...

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.